The method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6 - were) decanoas acid

 

The invention relates to an improved process for the preparation of ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid, which is an intermediate product, suitable for the synthesis of idebenone - drug nootropic action. The method comprises the hydrogenation of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid with hydrogen in the medium of organic solvent is a lower monohydroxy alcohol in the presence of palladium catalyst on a carbon carrier Sibunit, pre-treated isopropanole a sulfuric acid concentration of 0.3610-2KMOL/m3moreover , the hydrogenation is conducted at a stationary catalyst in the reaction zone continuously served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid in the amount of 1.6610-2- 8,310-2KMOL/m3and hydrogen under pressure 0,5-6,0 MPa with a feed rate of 0.510-8to 12.010-8m3/s Thanks to the creation of a continuous method, stimulating the process of obtaining large quantities of the desired product. 2 C.p. the Boo obtain the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid the intermediate product, suitable for the synthesis of idebenone - drug nootropic action. The invention can be used in the medical industry.

To create new technologies are more promising continuous processes, compared to the periodic possess a number of advantages: simplicity of design, continuity of work, the possibility of obtaining large quantities of the reaction products, ease of control.

A method of obtaining 10-(2-hydroxy-3,4-dimethoxy-6-were) decanoas acid by restoring the carbonyl group at the 9-(hydroxy-3,4-dimethoxy-6-methylbenzoyl) nonanalog acid in the medium of anhydrous acetic acid over 5% palladium on coal for 6.5 hours at room temperature, and then 6.5 hours at 50-60C. the Yield of the target product was 57% [K. Okamoto. M. Watanabe. etc.Chem.Pharm.Bull., 1982, v.30, No. 8, R. 2797-2819].

The disadvantage of this method is the length of the hydrogenation process, the low yield of the target product, using as solvent an environmentally unpromising anhydrous acetic acid, work in periodic mode.

The closest in technical essence is a way - ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid in the environment of isopropyl alcohol over 4% palladium on carbon carrier Sibunit, pre-treated isopropanol sulfuric acid solution. The process is carried out at temperatures of 30-60With, the process of hydrogenation of from 1 to 6 hours. The yield of the target product was 92-97% (RF patent No. 2118637, C 07 C 67/30, 69/734, 01 J 23/44, 1998).

The disadvantage of this method is its implementation in periodic mode, which limits the possibility of obtaining large quantities of the reaction product.

The objective of the present invention is the development of a continuous method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid using as a starting compound ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid.

The technical result is the intensification of the process of obtaining large quantities of the reaction product.

The technical result is achieved in that in the method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid comprising hydrogenation of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid with hydrogen in the medium of organic solvent is a lower monohydroxy alcohol in the presence of palladium catalyst on a carbon carrier Sibunit, pred-2KMOL/m, according to the invention, the hydrogenation is conducted at a stationary catalyst in the reaction zone continuously served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid in the amount of 1.6610-2-8,310-2KMOL/m3and hydrogen under pressure 0,5-6,0 MPa with a feed rate of 0.510-8-12,010-8m3/s. The hydrogenation is carried out at a temperature of 40-70C. the Catalyst used granulated with a palladium content of from 2 to 5%.

Compared with the prototype of the method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid is continuous, the starting materials into the reaction zone serves Autonomous concurrent threads.

A positive result of the proposed method is to obtain the target product with the release of 97-100%.

When processing catalyst isopropanole the sulfuric acid concentration is less than 0,3610-2KMOL/m3hydrogenation is slow, the output of the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid is small, the use of isopropylnaphthalene solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid concentration more 8,310-2KMOL/m3leads to reduction of the yield of ethyl ether 10-(2,3,4-trimetoksi-6-were) decanoas acid, and the concentration is less than 1,6610-2KMOL/m3leads to the formation of Perevedenovsky reaction products.

Changing the feeding speed of the original isopropanolic solution of ethyl ester 9-(2,3,4-trimethoxy-6-methylbenzoyl) nonanalog acid below 0.510-8m3/s and above 12.010-8m3/s reduces the output of the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid.

Conducting the process at a partial hydrogen pressure below 0.5 MPa reduces the yield of the target product. The increase in the partial pressure of hydrogen over 6,0 MPa leads to hydrogenation not only the carbonyl group in the ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid, and the benzene ring, the output of the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid decreases.

The use of stationary loaded granular catalyst allows to simplify the technological equipment of the process and provides the lowest loss of the catalyst during the hydrogenation.

The use of the catalyst and more than 5% is disadvantageous because of the increase in the content of the precious metal in the catalyst.

Carrying out the process at temperatures below 40With leads to a decrease of the yield of the target product, and above 70With the evaporation of the solvent is isopropyl alcohol.

The drawing shows a flow chart of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid.

To perform synthesis in the reactor 1 is placed stationary catalyst 2. In the lower part of the reactor 1 are carts initial products: P1 is the solution of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid, 2 - hydrogen. In the upper part of the reactor 1 are: P3 - out of the reaction mass containing the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid, and A4 is hydrogen.

Example 1. Fill the reactor granular catalyst Pd/Sibunit (2% Pd), pre-treated isopropanol sulfuric acid solution of 0.3610-2KMOL/m3. In the lower part of the reactor served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid concentration to 4.9810-2KMOL/m in isopropanol with a speed of 0.55 m3/s and a hydrogen pressure of 0.5 MPa and a temperature of 40the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid.

Example 2. Fill the reactor granular catalyst Pd/Sibunit (2% Pd), pre-treated isopropanol sulfuric acid solution of 0.3610-2KMOL/m3. In the lower part of the reactor served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid concentration of 8.310-2KMOL/m3in isopropanol with a speed of 3.33 m3/s and hydrogen under a pressure of 6 MPa to a temperature of 50C. the conversion of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid 98%. The product of synthesis is the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid.

Example 3. Fill the reactor granular catalyst Pd/Sibunit (2% Pd), pre-treated isopropanol sulfuric acid solution of 0.3610-2KMOL/m3. In the lower part of the reactor served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid concentration of 1.6610-2KMOL/m3in isopropanol with speed 11,85 m3/s and hydrogen under a pressure of 2 MPa at a temperature of 70C. the conversion of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylb the th acid.

Example 4. Fill the reactor granular catalyst Pd/Sibunit (2% Pd), pre-treated isopropanol sulfuric acid solution of 0.3610-2KMOL/m3. In the lower part of the reactor served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid concentration of 3.3210-2KMOL/m in isopropanol with speed 6,67 m3/s and a hydrogen pressure of 4 MPa, a temperature of 60C. the conversion of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl) nonanalog acid 99%. The product of synthesis is the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid.

Currently, the method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were) decanoas acid tested on pilot plant and prepares for industrial implementation.

Claims

1. The method of obtaining the ethyl ester of 10-(2,3,4-trimetoksi-6-were)decanoas acid comprising hydrogenation of the ethyl ester of 9-(2,3,4-trimetoksi-6-methylbenzoyl)nonanalog acid with hydrogen in the medium of organic solvent is a lower monohydroxy alcohol in the presence of palladium catalyst on uglerodsoderzhashchego src="https://img.russianpatents.com/chr/183.gif">10-2KMOL/m3, characterized in that the hydrogenation is conducted at a stationary catalyst in the reaction zone continuously served a solution of ethyl ester 9-(2,3,4-trimetoksi-6-methylbenzoyl)nonanalog acid in the amount of 1.6610-2- 8,310-2KMOL/m3and hydrogen under pressure 0,5-6,0 MPa with a feed rate of 0.510-8to 12.010-8m3/s

2. The method according to p. 1, characterized in that the hydrogenation is carried out at a temperature of 40-70C.

3. The method according to p. 1, characterized in that the catalyst used granulated with a palladium content of 2-5%.

 

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